CYTOKINE AND GROWTH-FACTOR REGULATION OF MACROPHAGE SCAVENGER RECEPTOR EXPRESSION AND FUNCTION

Regulation of macrophage scavenger receptor (MSR) activity may be an i mportant determinant of the extent of atherogenesis and the efficacy o f host defense. The effect of M-CSF on this pathway was studied using a recently developed monoclonal antibody to murine MSR. M-CSF markedly and selectively increased MSR synthesis in murine macrophages (M phi) ; post-translationally the receptor appeared more stable and shifted t o a predominantly surface distribution. Functionally M-CSF enhanced mo dified lipoprotein uptake and increased divalent cation-independent ad hesion in vitro. These results suggest a plausible mechanism whereby M -CSF production in the atheromatous plaque microenvironment could prom ote the recruitment and retention of mononuclear phagocytes and subseq uent foam cell formation. In addition, the Th1 cytokine (gamma-interfe ron) and Th2 cytokine (interleukin-4) had differential effects on MSR glycosylation in vitro suggesting a further possible regulatory role b y these lymphokines on macrophage MSR function.